Multifactorial Pathogenesis of Osteoporosis and the Role of Genes of Canonical WNT-Signaling Pathway

Майлян, Э. А.

doi:10.14341/osteo2015215-19

Cited by 3 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Канонический сигнальный путь отличается накоплением β-катенина в ядре клетки, который активирует факторы транскрипции (Т-клеточный фактор/лимфоидный фактор), модулирующие экспрессию генов-активаторов остеобластогенеза [ 43 ]. Синтез OPG также опосредуется сигнальным каскадом Wnt/β-катенин [ 44 ].…”

Section: остеопороз и муковисцидозunclassified

Cystic fibrosis being a polyendocrine disease (Review)

Chagay

Khayt

Вдовина

et al. 2021

Probl Endokrinol (Mosk)

View full text Add to dashboard Cite

The cystic fibrosis transmembrane regulator (CFTR) gene encodes the synthesis of a protein of the same name, which functions as a direct activator of anionic transport. Chloride is the most abundant anion; as an antagonist of Na+ and K+, it provides electroneutrality of cell membranes at rest; together with cations, it serves as an important osmolyte and forms water flow across cell membranes for transepithelial secretion.Glandular cells in CF trap Cl– and Na+, and the prodused secretion is excessively viscous. Subnormal CFTR activity leads to stagnation of mucociliary clearance, inhibition of intestinal transport.In addition to exocrine disorders, CFTR mutations are associated with a decrease in volume, mass, increased apoptosis of β-cells of the pancreas, a significant suppression of insulin exocytosis in response to stimulation with glucose and glucagon-like peptide-1, hyperglucagonemia against the background of a defect in the suppression of α-cell function by insulin, but a decrease in maximum capacity α-cells.Deficiency and progressive decline in bone mineral density is an expected secondary manifestation of CF due to pancreatic exocrine insufficiency with malabsorption of nutrients and fat-soluble vitamins. However, in patients with the F508del mutation, a significant decrease in the synthesis of OPG, COX-2, PGE2 in the osteoblastic formation, and an increase in the activity of the antianabolic NF-kB were found. We are talking about a defect in the canonical signaling pathway (Wnt/β-catenin), which regulates the expression of genes-activators of osteoblastogenesis, dissociation of the stages of physiological bone remodeling.In addition to congenital bilateral or unilateral aplasia of the vas deferens, an increase in the frequency of CFTR mutations is also found in non-obstructive azoospermia, oligo-, astheno- and teratospermia. CFTR is involved in the entry of HCO3– into Sertoli cells to trigger cAMP-dependent transcription and its defects lead to suppression of FSH-dependent gene expression of spermatogenesis, loss of sequence in the Wnt cascade, destruction of the PGE2-dependent transepithelial interaction and, as a consequence, the blood-testicular barrier.CF is characterized, along with classical signs, by endocrine dysfunction of the pancreas, osteoporosis with suppression of osteoblastogenesis, and a defect in spermatogenesis.

show abstract

Section: остеопороз и муковисцидозunclassified

Cystic fibrosis being a polyendocrine disease (Review)

Chagay

Khayt

Вдовина

et al. 2021

Probl Endokrinol (Mosk)

View full text Add to dashboard Cite

show abstract

IImmunological parameters in patients with chronic opisthorchiasis bearing gene mutations associated with osteoporosis-predisposition

Kurlaeva,

Stepanova,

Stepanova

et al. 2023

Russian Journal of Infection and Immunity

View full text Add to dashboard Cite

To identify the features of the immune system functioning in patients with chronic opisthorchiasis bearing mutations in loci associated with predisposition to developing osteoporosis, comprehensive studies of cellular and humoral arms were carried out. The state of the phagocytic system was assessed by assessing absorption, metabolic activity and reactive oxygen species formation to restore nitrosine tetrazolium (spontaneous and stimulated NST test). The phenotype of lymphocytes was determined by flow cytometry. The humoral immune arm was evaluated by the number of immunoglobulin classes M, G, A and E. Differences in the functional state of various arms of the immune system were revealed. In patients with chronic opisthorchiasis in the presence of rs1544410 polymorphism of the gene encoding the intracellular vitamin D receptor, the relative number of T-helper cells is significantly lower than in the group with the normal allele. In the presence of rs1800012 polymorphism of the gene encoding the 1-chain of type I collagen, the absolute lymphocyte count is significantly higher, spontaneous and stimulated NST test were lower, the number of DN-T lymphocytes is significantly lower (both in relative and absolute values). In the presence of the rs3736228 mutation of the gene encoding the transmembrane low-density lipoprotein receptor, the level of myeloperoxidase and the neutrophil stimulation index are lower, the absorption activity of neutrophils is higher. The presence of the rs2234693 mutation for estrogen receptor gene leads to significantly increased level of stimulated NST test and IgG concentration. Thus, patients with chronic opisthorchiasis bearing mutations in the COL1 A1, LRP5, ESR1(rs2234693) genes, have altered both nonspecific innate reactions and parameters of the adaptive immune arm; mutation of the VDR gene s9lely affects adaptive immunity. Analysis of the results suggests that the presence of mutations associated with the development of osteoporosis has a modulating effect on the immune response in chronic opisthorchiasis invasion. The identification of polymorphic genes associated with metabolic disorders of bone tissue and the study of the immunological profile in patients with chronic opisthorchiasis invasion will allow to implement an individual approach in the treatment of such patients.

show abstract

Role of Cytokines in Bone Tissue Remodeling in Norm and Pathology

Игнатенко

Maylyan

Немсадзе

et al. 2022

Tavricheskiy Mediko-Biologicheskiy Vestnik

View full text Add to dashboard Cite

Significant successes in the study of physiological and pathophysiological patterns of bone remodeling in recent years have highlighted immune factors important role in bone tissue pathology and significantly revised our ideas about postmenopausal osteoporosis development mechanisms. Advanced osteoimmunology and evidence of immune mechanisms key role in bone remodeling disorders gave us possibility for identification of osteoporosis as chronic immune-mediated disease. Moreover, instead of the term “Osteoporosis”, the term “Immunoporosis” was reasonably used. Bone tissue is constantly in state of continuous renewal (remodeling), which is balanced by formation and resorption processes and is achieved through the coordinated functioning of the three main bone cells types. Constant and active interaction between osteocytes, osteoblasts and osteoclasts is ensured by cytokines (RANKL, osteoprotegerin, macrophage colony-stimulating factor, vascular endothelial growth factor, etc) secretion. Moreover, predominantly, bone remodeling regulation is limited by Osteocyte-Osteoblast-Osteoclast system. With pathological changes in immune reactivity, which may be caused by deficiency of estrogen, vitamin D, calcium, inflammatory diseases, etc., various types of immunocompetent cells are activated. This is accompanied with increased RANKL production by leukocyte cells, which potentiates processes of maturation, differentiation of osteoclasts, and increase in their activity. In addition to RANKL secretion, activated leukocytes, including T lymphocytes, enhance other osteoclastogenic cytokines production. IL-1, IL-6, IL-17, TNF and TGF-β are main mediators of accelerated bone loss in postmenopausal women.

show abstract

Multifactorial Pathogenesis of Osteoporosis and the Role of Genes of Canonical WNT-Signaling Pathway

Cited by 3 publications

References 10 publications

Cystic fibrosis being a polyendocrine disease (Review)

Cystic fibrosis being a polyendocrine disease (Review)

IImmunological parameters in patients with chronic opisthorchiasis bearing gene mutations associated with osteoporosis-predisposition

Role of Cytokines in Bone Tissue Remodeling in Norm and Pathology

Contact Info

Product

Resources

About